Inhibitors of alternative alleles of genes as a basis for cancer therapeutic agents

Abstract

This invention is directed to a therapeutic strategy involving (1) identification of alternative alleles of genes coding for protein vital for cell viability or cell growth and the loss of one of those alleles in cancer cells due to loss of heterozygosity (LOH) and (2) the development of inhibitors with high specificity for the single remaining alternative allele of the vital gene retained by the cancer cell after LOH. The inhibitors of this invention are specific for one alternative allele of a gene that codes for a protein vital to cell viability or cell growth. The targeted gene has two alternative alleles in which the inhibitors of this invention blocks only one of the two alternative alleles, still present in the cancer cells. Exposure to the inhibitor inhibits or kills cancer cells which have undergone LOH. Protein is still capable of being expressed in the normal cells exposed to the inhibitor by the unblocked alternative allele. This differential effect of the inhibitor on cancer cells and normal cells accounts for the high therapeutic index of the inhibitors of this invention when used as antineoplastic agents.

What is claimed is: 
     
       1. A method for identifying a patient suitable for treatment with an allele-specific inhibitor, comprising the steps of: a) identifying a patient whose somatic cells are heterozygous for a gene essential for cell viability or growth; and   b) determining whether cancer cells of said patient are homozygous for said gene;   wherein homozygosity of said cancer cells for said gene is indicative that said patient is suitable for said treatment.   
     
     
       2. The method of claim 1, wherein said identifying comprises determining the genotype of said patient at polymorphic sites in said gene in somatic cells.